Therapeutic efficacy of artesunate-amodiaquine and artemether-lumefantrine and polymorphism in Plasmodium falciparum kelch13-propeller gene in Equatorial Guinea

Matilde Riloha Rivas (1) , Marian Warsame (2) , Ramona Mbá Andeme (1) , Salomón Nsue Esidang (1) , Policarpo Ricardo Ncogo (3) , Wonder Philip Phiri (4) , Consuelo Oki Eburi (1) , Corona Eyang Edú Maye (1) , Didier Menard (5, 6) , Eric Legrand (5, 6) , Pedro Berzosa (7) , Luz Garcia (7) , Angela Katherine Lao Seoane (8) , Spes Caritas Ntabangana (9) , Pascal Ringwald (9)

1 Ministry of Health and Social Welfare [Malabo, Equatorial Guinea]
2 GU - Göteborgs Universitet = University of Gothenburg
3 CSAI - Fundación Estatal, Salud, Infancia y Bienestar Social, F.S.P. [Madrid]
4 MCDI - Medical Care Development International [Malabo, Equatorial Guinea]
5 Génétique du paludisme et résistance - Malaria Genetics and Resistance
6 Biologie des Interactions Hôte-Parasite - Biology of Host-Parasite Interactions
7 Institute of Health Carlos III
8 WHO - World Health Organization-Country Office Equatorial Guinea
9 OMS / WHO - Organisation Mondiale de la Santé / World Health Organization Office

Background: Artesunate-amodiaquine (ASAQ) and artemether-lumefantrine (AL) are the currently recommended first-and second-line therapies for uncomplicated Plasmodium falciparum infections in Equatorial Guinea. This study was designed to evaluate the efficacy of these artemisinin-based combinations and detect mutations in P. falciparum kelch13-propeller domain gene (Pfkelch13). Methods: A single-arm prospective study evaluating the efficacy of ASAQ and AL at three sites: Malabo, Bata and Ebebiyin was conducted between August 2017 and July 2018. Febrile children aged six months to 10 years with confirmed uncomplicated P. falciparum infection and other inclusion criteria were sequentially enrolled first in ASAQ and then in AL at each site, and followed up for 28 days. Clinical and parasitological parameters were assessed. The primary endpoint was PCR-adjusted adequate clinical and parasitological response (ACPR). Samples on day-0 were analysed for mutations in Pfkelch13 gene. Results: A total 264 and 226 patients were enrolled in the ASAQ and AL treatment groups, respectively. Based on per-protocol analysis, PCR-adjusted cure rates of 98.6% to 100% and 92.4% to 100% were observed in patients treated with ASAQ and AL, respectively. All study children in both treatment groups were free of parasitaemia by day-3. Of the 476 samples with interpretable results, only three samples carried non-synonymous Pfkelch13 mutations (E433D and A578S), and none of them is the known markers associated with artemisinin resistance. Conclusion: The study confirmed high efficacy of ASAQ and AL for the treatment of uncomplicated falciparum infections as well as the absence of delayed parasite clearance and Pfkelch13 mutations associated with artemisinin resistance. Continued monitoring of the efficacy of these artemisinin-based combinations, at least every two years, along with molecular markers associated with artemisinin and partner drug resistance is imperative to inform national malaria treatment policy and detect resistant parasites early.

Mots clés: Artesunate-amodiaquine; Artemether-lumefantrine; Plasmodium falciparum; Efficacy; Equatorial Guinea; Artemether–lumefantrine

Domaines: Parasitologie

Matilde Riloha Rivas, Marian Warsame, Ramona Mbá Andeme, Salomón Nsue Esidang, Policarpo Ricardo Ncogo, et al.. Therapeutic efficacy of artesunate-amodiaquine and artemether-lumefantrine and polymorphism in Plasmodium falciparum kelch13-propeller gene in Equatorial Guinea. Malaria Journal, 2021, 20 (1), pp.275. ⟨10.1186/s12936-021-03807-x⟩. ⟨pasteur-03273687⟩